DESCRIPTION: This proposal focuses on the relation between the cell biology (localization,targeting) of trimeric G proteins and their ability to transduce signals. Experiments will: 1) Elucidate key steps in the localization mechanisms that target G protein alpha and beta-gamma subunits to the plasma membrane and determine where and when they become capable of transducing signals from the receptor to the effector. 2) Assess the role of G-alpha palmitoylation, a lipid modification that may serve to retain these subunits at the plasma membranes and determine how these mechanisms modulate G protein mediated signals inintiated by receptor agonists. 3) Identify cellular proteins that associate with G-beta-gamma subunits and mediate cellular proliferation and (potentially) neoplastic transformation via activation of the MAPK/ERK pathway. 4) Define interactions of the G-alpha with three proteins - actin, caveolin and members of the G-alpha-interacting protein (GAIP) family-that may inhibit G protein signaling by interacting with and sequestering G-alpha subunit.